Posts Tagged ‘influenza’

The Center for Disease Control and Prevention, AKA the CDC, America's central medical laboratory has recently had multiple problematic episodes. I was trying to follow up on the vials of smallpox virus that were found in an old refrigerator that the FDA apparently had forgotten, The question, of course, was whether the virus samples were long dead or still viable. They had been sent to the CDC to have that highly significant issue resolved.

Since then there has been a followup announcement, but also several articles on significant issues with procedures and safety at the CDC itself. The first was published in The New York Times, AKA NYT, (as well as in other papers, but I get the NYT daily on my iPad , so saw it there first). The startling title was "C.D.C. Closes Anthrax and Flu Labs after Accidents." The current director of the CDC, Dr. Thomas Frieden, called the lab/agency "the reference laboratory to the world," but admitted there had been a series of accidents (actually lapses in set safety procedures), in the recent past, that were quite frightening.

A month ago potentially infectious samples of anthrax, a bacteria found naturally in soil and commonly affecting wild and domesticated animals worldwide, causing an extremely serious, but rare illness in people, were sent to labs that were not equipped to deal with them (anthrax would normally be handled only with the highest level of protective biosafety gear and procedures (BSL-4). The CDC also has a rather simplistic YouTube video discussing anthrax's use as a potential bioterrorism weapon, but in this case 62 or more CDC employees were potentially exposed to the bacteria in the course of their work.

The good news is it appeared nobody was in danger; all those employees were given the anthrax vaccine and also begun on antibiotics. The background information available online says there has never been person to person spread of the disease.

It appears that it's exceedingly tough to get rid of anthrax in the environment; I'll go over the classic historical example of how careful government researchers have been with its spores..

In the 1940s, British scientists used a small Scottish island (Gruinard) for germ warfare research. That island, thoroughly contaminated with anthrax spores, remained off-limits for forty+ years before extraordinary efforts, begun in 1986, rendered it safe for ordinary use. The surface of the island was only 484 acres; it was sprayed with a herbicide, then all dead vegetation was burned off. Next 200 tons of formaldehyde solution was diluted in 2,000 tons of seawater and sprayed over the entire island. Perforated tubing was used to ensure that 50 liters of solution were applied to every square meter being treated.

Later the effectiveness of the decontamination process was assessed by taking two duplicate sets of soil samples. Each was tested at two major government labs. Anthrax spores were detected only in "small quantities in a few places." These specific areas were treated in July 1987, followed by further soil sampling in October 1987. No further traces of anthrax spores were found.

Blood samples from local rabbits were also tested for anthrax antibodies. No such antibodies were found.

Following these measures, a farmer grazed part of his flock of sheep on the island for six months. The sheep were inspected monthly by the District Veterinary Officer, and returned to the mainland in October 1987 in excellent condition.

On April 24, 1990, 4 years after the decontamination works had been completed, a Defense Minister visited the island and removed the safety signs, indicating that the island had finally been rendered safe. Then, per agreement the island was sold back to the heirs of the original owner for the WWII sale price of £500.

But a senior British archeologist said he still wouldn't set foot on the island; he was concerned because of potentially infectious particles found in some of his digs.

Yet another NYT piece, "Ticking Viral Bombs, Left in Boxes," this one written by a distinguished physician, Lawrence K. Altman, M.D. recalls the irony of the outcry for mass smallpox vaccination of our entire U.S. population after 9-11 (when no Iraqi supply of the deadly bacterium was ever located), contrasted with the recent finding of six vials, two with live smallpox bugs, being found in in Bethesda, almost within "spitting distance" of our center of government.

In 2011 the Birmingham Mail reviewed a tragic lab accident which led to the last known smallpox death . The city, now England's second largest, was a site of a medical research laboratory associated with the local medical school. Viral particles got into an air duct and a photographer whose studio was one story up from the lab became the last known case of active smallpox and died from the disease in spite of having been vaccinated twelve years before

Dr. Altman discusses the pros and cons of eradicating the last two known stocks of the virus, one at the CDC, the other in a Russian lab in Siberia. Even if the natural virus is finally and totally eliminated , a rogue group may well be able to re-establish their own supply from the known genetic sequence of smallpox.

Lastly I saw a NYT article with an even more disturbing title, "After Lapses, C.D.C. Admits a Lax Culture at Labs." CDC workers had somehow shipped a dangerous strain of avian influenza to a poultry research lab run by the Department of Agriculture. Known as H5N1, the virus had killed more than half of the 650 people who had been infected with it since 2003. Again there were no deaths from this mistake.

After all of this recent furor plus the historical examples, I'm heartily in favor of the idea that's been broached saying such dangerous organisms should be confined to a minimal number of labs and even those clearly need to tighten up their standards.

Like we always do, we got our flu shots early, this year on the day after they first became available. Several friends said they were going to wait a few months; I'm always concerned that the supply of vaccine will be gone by then and as former Air Force medical staff, we got in the habit of being told, "It's time for your flu shot." Our timing was excellent; flu struck earlier than usual (it typically peaks in February). And the New York State Department of Health agreed that the best time to get a flu shot is as soon as the vaccine is available.

This is a bad flu season with not only an early peak in case numbers, but also an unusual virus. I looked at the flu primer, updated for the 2012-2013 season, by arstechnica, a technology news and information website. The influenza virus has an outer layer of proteins around its genetic material core; the specific proteins of the coating determine what kind of cells the flu bug can attach to and therefore infect (they also act as chemicals that our immune system can react to), while the inside core lets the virus take over the cell and make new viral particles.

flu virus with Hs and Ns sticking out; I think of them as arms and legs

The most important proteins in the outside coating are called hemagglutinin (H) and neuraminidase (N); there are a variety of each with the CDC saying there are 16 different Hs and 9 Ns. Three variants, H1N1, H1N3 and H3N2, are currently infecting humans while the highly pathogenic H5N1 avian flu was of major concern in recent years. As of January 5th, 2013, the influenza A H3N2 virus was the predominant strain causing flu in the United States.

There are three types of influenza viruses, logically enough labeled types A, B and C. Type A can affect both humans and some animals and is responsible for the largest and most widespread outbreaks termed pandemics. Type B only occurs in people and usually is responsible for less severe reactions; it is not classified by subtypes and isn't responsible for pandemics. Type C, also only a human strain, doesn't cause epidemics, much less pandemics and doesn't lead to severe illness. The yearly vaccine protects against two type A strains (H1N1 and H3N2) and one type B virus with specific viruses chosen based on scientific estimations of what the coming year's flu will most likely be. The CDC webpage titled "Key Facts about Seasonal Flu Vaccine" mentions three different flu shot varieties and one nasal vaccine; the shots are all made from inactivated viruses (one is a high-dose form designed for those of us 65 and older). The nasal spray is made from live attenuated (weakened) viruses and can be given to anyone age 2 to 49 who is not pregnant and is otherwise healthy.

Now civilian hospitals in a number of areas have fired staff members who refused to get vaccinated for influenza. Some of those former hospital employees are threatening to sue, but my own viewpoint is the hospitals have done the right thing. The last thing I think they need is their own docs, nurses, techs and other staff infecting patients who are already ill with something that may make them more likely to have flu complications.

What about pregnant women who work for the hospital? Should they get flu shots or does that place their fetuses at risk? I wasn't sure until I saw the 1-16-2013 edition of the New England Journal of Medicine. A Norwegian study performed during the 2009 flu pandemic had convincing figures: there were 117,347 eligible pregnancies and 54% of the women were vaccinated in their second or third trimester with substantial reduction in moms getting the flu.

Pregnant women in this study who did have influenza had an increased risk of fetal death. Vaccination did not increase fetal mortality (and may actually have reduced it).

epidemics are many more cases than usual; pandemics have widespread cases

The real problem with bad cases of flu is bacterial coinfection, often with "bugs" that colonize our nasopharynx area: staph aureus, strep pneumoniae and strep pyogenes. This highly significant flu complication was present in almost everyone who died in the great flu pandemic in 1918 and, even today, with our panoply of antibiotics, frequently occurs in influenza victims who require ICU care. A third of those needing such intensive care in the 2009 H1N1 pandemic had such a combined illness.

many other major pandemics were associated with rodents, but not the 1918 flu

I re-read my last post a day after writing it and amended the first line, since I found it misleading. It was the worst flu pandemic ever, but I knew that smallpox, the Black Plague, AIDS, malaria and perhaps even typhus each have caused nearly as many or even more deaths over a period of years. I eventually found a rather strange, non-medical website with the "7 Worst Killer Plagues in history," and confirmed my belief that no other bacteria or virus had wreaked as much havoc in brief span of time as the 1918-1919 H1N1 influenza virus.

I wanted to find out what happened to that highly pathogenic organism and, after searching the web, realized the PBS article on the "Spanish flu" was a good place to start. It mentions that the influenza virus was not identified until 1933 and that the actual genetic identity of the particular strain involved in that pandemic (as opposed to the basic type...H1N1) was not identified for many years. The influenza virus responsible for the 1918-1919 pandemic has had many descendants, none as deadly as their ancestor.

In 1950, Johan V Hultin, a graduate student starting his doctoral studies in microbiology, got a clue from a visiting professor who suggested hunting for the virus in bodies buried 32 years prior in the permafrost of the Arctic. Hultin and his faculty advisor traveled to Alaska where flu among the Inuits had been especially deadly with 50 to 100% death rates in five villages.

early days in the Far North

Gold miners, under contract with the Territorial government, had served as grave diggers in 1918-1919 and tissue samples were recovered from four bodies exhumed in 1951. Pathology slides fit with viral lung damage and, in some cases, secondary bacterial pneumonia. But tissue cultures from the samples did not cause disease in ferrets and no influenza virus was recovered.

It wasn't until 1995 that science had advanced enough to for researchers to start the work necessary to identify the virus's unique features. Jeffrey Taubenberger, a molecular pathologist then working at the Armed Forces Institute of Pathology (AFIP), began a ten-plus-year-long project starting with autopsy tissues from the time of the pandemic that had been preserved in the National Tissue Repository. His project was stimulated by a paper published in the journal Science in February, 1995, in which preserved tissue samples from the famous British scientist John Dalton (often called the father of modern atomic theory) were examined. Dalton was color-blind and had donated his eyes at his death in 1844 to determine the cause of the defect; his DNA was studied 150 years later and the resultant publication gave Taubenberger the impetus to do the same with the flu virus.

Hultin read the first paper from Taubenberger's group, wrote to him and eventually went back to Alaska to exhume more flu victims. One was an obese woman whose lungs had the findings of acute viral infection. Samples of these permafrost-preserved tissue had RNA incredibly similar to those obtained from the AFIP National Tissue repository.

Most of us who are adults (and many who are not) have personal knowledge of human sexual reproduction, the process by which a man and a woman each contribute genetic material that contains DNA (deoxyribonucleic acid), the chemical basis of new life. DNA is an incredibly long twisted molecule. Its structure is a double helix with two strands composed of a sugar-phosphate backbone linked by four specific chemicals: adenine (A), thymine (T), cytosine (C) and guanine (G). These are called bases and match up in specific pairs, A always with T and G with C.

DNA has an amazing ability to replicate itself; the strands separate and each becomes the pattern for a duplicate to be constructed. Occasional mistakes are made, but we have a cleanup chemical, DNA polymerase, a kind of automatic spellchecker, that makes corrections.

Our human DNA has about 3 billion pairs of these bases; yours and mine and Cousin Flo's will be 99% identical. The remaining 1% is what makes the difference between an Einstein, a sports hero, a jazz musician and you and me. Our DNA is 98% the same as a chimpanzees and 85% the same as a mouse, but these comparisons clearly understate the importance a single base pair difference can make.

Viral "reproduction" is quite different. Influenza viruses don't have DNA; instead they contain RNA and have to replicate in living cells. Once they are inside one, the process results in many viral "offspring." These eventually leave to infect other cells in the organism and in doing so kill the one they replicated in. RNA (ribonucleic acid) is somewhat like DNA, but has one different base and a slightly different sugar in its "backbone." It's usually found as single strands shorter than those of DNA or, in the case of the flu virus, in seven or eight pieces. It lacks a proofreading enzyme so most of the new influenza virus copies are actually mutants.

Most of these changes, called antigenic drift, are minor. So the flu shot I get every year, which is an educated best guess as to what this years flu virus will be, offers considerable, but not total protection.

flu shots make sense

Sometimes the mutations are more significant; the process is called antigenic shift. That may occur when a host is infected with two different influenza viruses at the same time. The swine flu, for example, contained genes from pigs, humans and birds. When this happens, pandemics may occur.

Influenza is spread in several different ways: an infected person coughs or sneezes and you inhale the aerosolized virus; humans may come into direct contact with bird droppings or nasal secretions; various surfaces may become contaminated (viral particles in mucous may survive several weeks on banknotes).

Modern techniques for producing new flu vaccines rapidly may prevent millions of deaths and steps toward a "universal flu vaccine" are being researched. In the meantime logical precautions and yearly flu shots can save lives.

I realized, as I wrote my last post, that I was using medical jargon that might make no sense to most readers. So I want to examine how the influenza virus is described by doctors, specialists in epidemics (AKA epidemiologists) and other scientifically-trained groups.

First of all let's briefly talk about how we classify everything that is alive. There's a complex system called taxonomy which is conventionally used to group separate different groups of dissimilar and similar organisms. It has seven major layers, or taxa. Humans, for example, belong to the kingdom Animalia, the phylum Chordata, the class Mammalia, the order Primata, the family Hominidae, the genus Homo and the species Homo sapiens.

Flu viruses fall into three genuses, and those logically enough are called A, B and C. The A type has only one species, lives in nature in wild aquatic birds (but can infect other animals), and causes the most severe diseases in humans. Subtypes of flu A can be identified by a variety of laboratory tests that determine which kind of two glycoproteins (complex chemicals that contain both carbohydrate and protein constituents) are found on the surface of the virus.

One of those is called hemagglutinin (H for short) and the other neauraminidase (N). There are 16 H types and 9 Ns; Hs bind the virus to a cell and help it insert its genetic information into that cell. Ns get involved later in the infection and help the virus release its "offspring" from the cells they were produced in.

Laboratory tests can show which H and N are present. Both are antigens, substances that can cause an immune reaction if taken into your body by one route or another (e.g., breathing them in) and cause your body to produce antibodies, chemicals that are produced to combine with and counter the effects of the antigen. Some important influenza viruses are H1N1 which caused the 1918 Spanish Flu and the 2009 Swine flu, H2N2 (Asian flu of 1957), H3N2 (Hong Kong Flu 1968) and H5N1 (Bird Flu in 2004).

The CDC's short article on types of influenza viruses mentions there are seasonal epidemics nearly every winter in the United States; those are caused by type A or B, not by type C. All of the terrible flu pandemics have been caused by type A flu viruses. The B virus types are normally found only in humans (seals and ferrets are the only other animals that can be infected by flu B).

We get ours every year

Why is type A the killer? It mutates much more rapidly than B, usually by minor changes in the H and N surface proteins, occasionally by sudden major changes. The first kind of change may alter the antigens you can be exposed to so the antibodies you've developed to fight off a flu infection don't work. That's also why the vaccine you get, which contains two A subtypes and one B strain, may not fully protect you. That's not a reason to skip your flu shot.

The other kind of mutation is more serious and I'll write about it next.

Two days ago I began a post on zoonoses, diseases that spread from animals to humans. As usual, my interest led me from one fairly-limited topic to more-generalized subjects and I eventually decide to write a multi-post discussion of viral diseases that either have caused massive, widespread epidemics (AKA pandemics) or could potentially lead to them.

The number of deaths they have resulted in is staggering. HIV/AIDS has killed over 25 million of us in the past 30 years; the Black Plague over a 330-year period killed 75 million and smallpox is estimated to have caused over 300 million deaths over the centuries.

But let's start with influenza, the virus that we read about year after year as a worldwide threat. In the fall my wife and I get flu shots; we got used to doing so when we were both on active duty as Air Force medical staff personnel. It was routine; I didn't pay a lot of attention to what this year's shot contained and only vaguely kept up with anything written about the flu itself.

Then so-called "bird flu" came along and the world geared up for a terrible pandemic.Usually the kind of influenza virus found in birds doesn't infect humans. But one unusual strain, called H5N1 (I'll explain what that means later) killed a six-year-old boy in Thailand in 2003. Of the people who caught this virus, 60 % died.

Most of us have heard about the Spanish flu, a major pandemic that infected a third of everyone living in 1918-1919 and caused 20 to 40 million deaths worldwide. Yet only 3% of those whom the virus infected died from it.

The so-called Asian flu pandemic in 1956-1958 causes 2 million deaths; the Hong Kong flu in 1968-1969 killed 1 million and the yearly seasonal flu results in anywhere from 5 to 15% of us getting ill; 250,000 to 500,000 die as a result. But these flu strains actually only resulted in a death ratio of less than 0.1%.

As it turned out, there was very little person to person spread of the avian flu. If there had been the results could have been catastrophic.

But the pigs had nothing to worry about; we did!

One of the outcomes of the avian H5N1 outbreak was fortuitous. When the "Swine flu" pandemic occurred in 2009-2010, the public health establishment and the medical community were considerably better prepared. The CDC summary is worth reading as it documents the steps taken to contain the virus; actually this was a flu strain that was transmitted from person to person and wasn't present in US pig herds.

The virus itself had genes from four different influenza virus sources, two from pigs, one from birds and one from a human flu virus. The CDC widely distributed kits to labs enabling them to identify the new viral strain. They and the World Health Organization (WHO) kept tabs on the numbers of cases of the new disease and WHO announced a global pandemic in June, 2009 .

A vaccine was developed with unusual speed and a preliminary target group of higher-risk individuals was identified; this consisted of 159 million people in the US. Vaccine safety was tested in various groups and the vaccine itself was administered starting in early October; by late December 2009 enough had been produced to allow vaccination of anyone wishing it.

The final results were impressive; less than two-thirds of a million people caught the virus and the death rate was 0.03%

I read two NYT articles about medical diseases that conflate to a really frightening juncture. They led me to find background data from a medical website and to do a Google search on one lead author.

Let's start with MRSA, the acronym for methicillin-resistant Staphylococcus aureus. Roughly 25% of us are staph carriers, but only 2% of us carry MRSA, the antibiotic resistant form that causes deadly complications so frequently and is so difficult to treat. Infections with "ordinary" staph bacteria can be very serious, but respond, in most cases, to the drugs commonly used. The NIH has an excellent summary of MRSA issues and I'll paste in a link to it below.

An August 11, 2011 NYT article mentioned that MRSA skin infections occur in those more prone to cuts and scrapes: athletes, the military and our kids among them. A professor of Medicine and Pediatrics at UC Davis Medical School is quoted as saying, "...in most communities, community acquired MRSA has become the dominant cause of soft tissue infection requiring emergency department care and inpatient care."

In a previous post I noted that a neighbor ended up in our local ICU for a prolonged stay after a scape on his elbow resulted in a rapid spread of redness up his arm unto his chest. As you might surmise, this was an MRSA-caused illness.

MRSA is a major urgent medical problem; almost 19,000 people died from this dire staph in 2005. In that timeframe most MRSA infections were felt to occur in immunocompromised patients.

But now hospital admissions for skin infection in kids have climbed; the rate of these more than doubled between 2000 and 2009. The overall rate still seemed low, 9.4 cases per 10,000 children, but that translates into just under 72,000 kids being hospitalized in that one year.

In the average year roughly 4,000 kids wind up in pediatric ICUs yearly because of severe flu infections and of course many times as many have mild cases of flu. The current study, headed by an associate professor of Anesthesia at Harvard, looked at children who got flu infections during the 2009-2010 H1N1 epidemic and were admitted to ICUs in 35 different locations. Of those 838 youngsters, nearly nine percent, 75 of those kids, died; their median age was 6.

More than a quarter of the children in the study were previously considered totally healthy; they didn't have asthma or a neurological disease; they were not immunosuppressed and didn't have other chronic conditions. So of the total, 251 kids were otherwise healthy prior to getting the flu; 18 of them died. The only predictor of death in healthy children in this group was MRSA infection; if they had this co-existing risk factor their risk of dying increased eight times when compared to those who did not have MRSA.

Please ask your pediatrician about flu vaccination

My take on the study, and that of the lead researcher, is it's time to make sure our kids and grandkids get vaccinated for flu on a yearly basis. There are still people who never want their children vaccinated; physicians in almost all cases would disagree with them.